Fertility and folic acid and zinc supplementation in men

A large-scale clinical trial of dietary supplementation in couples being treated for infertility shows that taking folic acid and zinc does not increase sperm quality or live birth rates. The findings are from the Folic Acid and Zinc Supplementation Trial.

Methods
Published in JAMA, the results are based on analysis of patients at four US reproductive endocrinology and infertility care study centers from June 2014 to December 2017. The researchers block randomized 2,370 men aged ≥ 18 by study center and planned infertility treatment to either 5 mg of folic acid and 30 mg of elemental zinc or placebo daily for 6 months. Infertility treatments included in in vitro fertilization, other treatment at a study site, and other treatment at an outside.

Ultimately 1,773 men were included in the final analysis, all of whom attended the final 6-month study visit. At 6 months after randomization, semen was available for analysis from 1,629 men. 

Findings
The authors found that there was no significant difference in live birth rates between the treatment and placebo groups (34% treatment; 35% placebo; risk difference -0.9%; 95% CI -4.7% to 2.8%). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) wee not significantly different between treatment groups at 6 months after randomization. 

The researchers did note a statistically significant increase in DNA fragmentation in the men who received folic acid and zinc supplementation (mean of 29.7% for percentage of DNA in the folic acid and zinc supplementation group and 27.2% in the placebo group; mean difference, 2.4% [95% CI 0.5% to 4.4%]). The authors said further research is necessary to assess the clinical importance of the DNA fragmentation finding.

Gastrointestinal symptoms were more common in the men taking the supplements than in the placebo group (abdominal discomfort or pain 66 [6%] versus 40 [3%], respectively; nausea 50 [4%] versus 24 [2%]; and vomiting 32 [3%] versus 17 [1%]).

Conclusions
Looking at secondary outcomes, supplementation had no significant effect on β-human chorionic gonadotropin-detected pregnancy, clinical intrauterine pregnancy, ectopic pregnancy, multiple pregnancy, early pregnancy loss, cesarean delivery, preeclampsia or gestational hypertension, gestational diabetes, gestational age, birth weight, or small for gestational age at birth. Supplementation was, however, associated with a statistically significant increase in preterm delivery overall (67 [6%] versus 45 [4%]; risk differenc 1.9% [95% CI 0.2% to 3.6%]).